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Interleukin-2 regulation of mucosal inflammation

IL-2对粘膜炎症的调节

基本信息

批准号：
10620278
负责人：
Gregory F Sonnenberg
金额：
$ 54.34万
依托单位：
WEILL MEDICAL COLL OF CORNELL UNIV
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-06-06 至 2025-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10620278
关键词：
Acute Address Affect American Antigen Presentation Antigens Biological Chronic Clinic Clinical Crohn&apos s disease of the ileum Data Development Disease Distal part of ileum Food Hypersensitivity Gastrointestinal tract structure Health Care Costs Homeostasis Human Hypersensitivity IL1R1 gene Immune Tolerance Immune response Immunity Immunologics In Vitro Inflammation Inflammatory Inflammatory Bowel Diseases Interleukin-1 beta Interleukin-2 Intestines Investigation Knowledge Large Intestine Location Lymphoid Cell Lymphoid Tissue Malignant Neoplasms Mammals Microbe Mucositis Mucous Membrane Mus Pathogenesis Pathway interactions Patients Phenotype Production Regulation Regulatory T-Lymphocyte Reporter Research Research Proposals Role Seminal Small Intestines Source T-Cell Activation T-Lymphocyte TSLP gene Therapeutic Tissues cytokine dietary graft vs host disease gut inflammation human disease in vivo innovation loss of function mutation microbial microbiota mucosal site novel novel strategies oral tolerance prevent response tool

项目摘要

PROJECT ABSTRACT Uncontrolled inflammation at mucosal sites underlies the pathogenesis and progression of multiple chronic human diseases including allergy, hypersensitivity, inflammatory bowel disease (IBD), cancer and graft-versus- host-disease (GVHD), and there is an urgent need to develop novel approaches to prevent, limit or reverse mucosal inflammation. Interleukin-2 (IL-2) is a pleiotropic cytokine that profoundly influences immunologic tolerance in mammals, and modulation of IL-2 is currently being developed as a therapeutic approach in the clinic. Since its discovery, a majority of research has focused on how IL-2 influences T cell activation or supports regulatory T cells (Tregs) within lymphoid tissues. Despite these advances, the critical cellular sources and functional regulation of IL-2 production at mucosal sites remains poorly defined. The fundamental focus of this research proposal is to interrogate novel cellular sources of IL-2 that critically influence immunologic homeostasis and inflammation within the mammalian gastrointestinal (GI) tract. We will employ innovative approaches and develop new tools to define the role and regulation of mucosal IL-2 during homeostasis or following intestinal inflammation and food allergy. Collectively, results from these studies will define the regulation and functional significance of novel cellular sources of IL- 2 within the intestine. These findings will critically inform ongoing therapeutic approaches to augment IL-2, or provoke the development of novel tractable strategies to promote tolerance and control mucosal inflammation.

项目摘要粘膜部位的不受控制的炎症是多发性慢性炎症的发病机制和进展的基础。人类疾病，包括变态反应、超敏反应、炎性肠病（IBD）、癌症和移植物抗宿主病（GVHD），迫切需要开发新的方法来预防，限制或逆转粘膜炎症白细胞介素-2（IL-2）是一种多效性细胞因子，对机体的免疫功能有着深刻的影响。目前正在开发IL-2的调节作为哺乳动物中的治疗方法。诊所自发现以来，大多数研究都集中在IL-2如何影响T细胞活化或支持淋巴组织内的调节性T细胞（TCLs）。尽管有这些进步，关键的细胞粘膜部位IL-2产生的来源和功能调节仍然不清楚。的这项研究的基本重点是研究新的IL-2细胞来源，严重影响哺乳动物胃肠内的免疫稳态和炎症 (GI)道。我们将采用创新的方法和开发新的工具，以确定稳态期间或肠道炎症和食物过敏后的粘膜IL-2。总体而言，成果从这些研究中将确定新的细胞来源的IL-1的调节和功能意义。 2在肠道内这些发现将为正在进行的治疗方法提供重要信息， IL-2，或引发新的易于处理的策略的发展，以促进耐受性和控制粘膜炎症。

项目成果

期刊论文数量（13）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Metabolic control of innate lymphoid cells in health and disease.

对健康和疾病中先天淋巴样细胞的代谢控制。

DOI：
10.1038/s42255-022-00685-8
发表时间：
2022-12
期刊：
NATURE METABOLISM
影响因子：
20.8
作者：
Zhou, Lei;Lin, Qingxia;Sonnenberg, Gregory F.
通讯作者：
Sonnenberg, Gregory F.

ILC3s control airway inflammation by limiting T cell responses to allergens and microbes.

DOI：
10.1016/j.celrep.2021.110051
发表时间：
2021-11-23
期刊：
Cell reports
影响因子：
8.8
作者：
Teng F;Tachó-Piñot R;Sung B;Farber DL;Worgall S;Hammad H;Lambrecht BN;Hepworth MR;Sonnenberg GF
通讯作者：
Sonnenberg GF

Group 3 innate lymphoid cells produce the growth factor HB-EGF to protect the intestine from TNF-mediated inflammation.

DOI：
10.1038/s41590-021-01110-0
发表时间：
2022-03
期刊：
Nature immunology
影响因子：
30.5
作者：
Zhou L;Zhou W;Joseph AM;Chu C;Putzel GG;Fang B;Teng F;Lyu M;Yano H;Andreasson KI;Mekada E;Eberl G;Sonnenberg GF
通讯作者：
Sonnenberg GF

In Situ Support of ILC Precursors.

ILC 前体的现场支持。